Approximately 7.9 million Americans suffer from heart failure every year. Among these, nearly 2.5 million develop Ischemic Mitral Regurgitation (IMR), a 33% increase since 1995. Even with such high prevalence, little is known of the cause and progression of chronic IMR, resulting in the current lack of effective medical options for these patients. What is known for certain is that IMR is secondary to gross three dimensional geometric alterations of the patient's Left Ventricle (LV), resulting in alterations in the geometry of the Mitral Valve (MV). Present surgical repair techniques to restore native LV and MV geometries lack satisfactory long-term patient outcomes. Consequently, long-term survival rates for IMR are poor and worse as compared to many types of cancer. The most important reason for the poor outcome is the lack of knowledge of the exact 3D geometric alterations of the patient's MV responsible for IMR, without which appropriate surgical treatment is not possible. The objective of this proposal is to delineate and understand the geometric distortions of the MV that lead to IMR and develop appropriate repair procedures that can be directly translated to clinical practice in the near future. The central hypothesis driving our long objectives is: Ischemic Mitral Regurgitation is strongly related to geometric alterations of the native mitral valve at the annular and/or sub-valvular levels. Understanding these alterations will clarify the geometric determinants of Ischemic Mitral Regurgitation and will help in designing better and efficient repair procedures thus leading to better surgical outcomes. Our hypothesis has been formulated based on strong preliminary data produced in our laboratories at Georgia Tech and the University of Pennsylvania. The proposed study consists of a sophisticated methodology combining in-vitro and in-vivo approaches to design an efficient IMR model that can not only test the hypothesis but also develop novel surgical approaches. The in-vivo model of IMR though effective is very reproducible and mimics only one representation of the human IMR disease. The in-vitro IMR model is a versatile model that provides precise control over the geometric distortions imposed on the valve. Also, the in-vitro model will be a potential test-bed with additional studies (beyond the currently proposed 2 year experiments) for developing novel MV surgical repair techniques that may be easily translated to clinical practice.